In order to elucidate metabolic functions of polyunsaturated fatty acids and phospholipids in nervous tissues, two aspects were studied: (i) Oxygenation of the two major polyunsaturates in brain, docosahexaenoic acid (22:6n3) and arachidonic acid (20:4n6); (ii) Molecular remodeling of phospholipids in brain tissues. When oxygenation of polyunsaturates by various regions of rat brain, including pituitary, hypothalamus, thalamus, cerebral cortex, cerebellum and pineal body was examined, only the pineal body was found to possess lipoxygenase activity. Both 20:4n6 and 22:6n3 were metabolized by pineal body homogenate, primarily through 12- but also 15-lipoxygenase reaction. The resulting metabolites were also detected in the pineal body lipid extract, possibly indicating endogenous production of these compounds. 15-lipoxygenase products were the major ones present in the lipid extract of pineal body, suggesting compartmentalization of the LO enzymes. Preliminary results indicated that the level of 17-hydroxy 22:6n3 in the pineal bodies of ethanol treated animals was increased by 50%. In order to understand the means by which 22:6n3 or 20:4n6 fatty acid is concentrated in certain lipid classes in brain, phospholipase (PLA) and phosphatidylserine (PS) decarboxylase were examined. Myelin, synaptosomal membranes and mitochondrial fractions were prepared, and among these only the mitochondrial fraction contained significant PLA2 and PS decarboxylase activities. Furthermore, in rats exposed to ethanol inhalation for 14 days, an increase in PLA2 activity of approximately 70% was observed in the brain mitochondrial fraction. Also, alcohol-induced losses of 20:4n6 and 22:6n3 was observed in a non-extractable fraction which was associated with membrane proteins.